1-Methylpiperazine → 2-Fluoro-4-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)aniline
Reaction equation
Br[C:2]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:5]([NH2:6])=[C:4]([F:13])[CH:3]=1.[CH3:14][N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.CC([O-])(C)C.[Na+]>C1COCC1>[F:13][C:4]1[CH:3]=[C:2]([N:18]2[CH2:19][CH2:20][N:15]([CH3:14])[CH2:16][CH2:17]2)[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:5]=1[NH2:6]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 120 °C
Procedure
To a microwave reaction tube was added 4-bromo-2-fluoro-5-(trifluoromethyl)aniline (256 mg, 1.0 mmol), 1-methylpiperazine (300 mg, 3 mmol) Pd2(dba)3 (91.5 mg, 0.1 mmol), di-tert-butyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (60 mg, 0.2 mmol), NaOtBu (144 mg, 1.5 mmol) and THF (3 mL). After the reaction tube was degassed and filled with N2, the tube was heated to 120° C. in a microwave reactor for 40 min. The mixture was then poured into saturated NH4Cl aqueous solution (10 mL) and extracted with EtOAc (3×10 mL). The organic layers were combined and concentrated. The residue was purified by flash column chromatography (silica gel, gradient MeOH/CH2Cl2, 0˜10%) to provide 2-fluoro-4-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)aniline as a white solid. ESMS m/z 278.1 (M+H+).
Workup
- customTo a microwave reaction tube
- customAfter the reaction tube was degassed
- additionfilled with N2
- additionThe mixture was then poured into saturated NH4Cl aqueous solution (10 mL)
- extractionextracted with EtOAc (3×10 mL)
- concentrationconcentrated
- customThe residue was purified by flash column chromatography (silica gel, gradient MeOH/CH2Cl2, 0˜10%)
Sources & evidence
- ORD record
- ord-a88f0a42c7d64b8a87cd433d9479196c
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08859574B2
Reaction notes
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